Proteomic profiling of human cancer pseudopodia for the identification of anti-metastatic drug candidates

Cancer metastasis causes approximately 90% of all cancer-related death. Independent of the advancement of cancer therapy, a majority of late stage patients suffers from metastatic cancer. Metastasis progresses by cancer cell migration and invasion throughout the body. This migration of cancer cells requires the formation of pseudopodia in the direction of movement, but detailed understanding of the process and accordingly strategies of prevention remain elusive. Here, we use quantitative proteomic profiling of human cancer pseudopodia to examine this mechanisms essential to metastasis formation, and identify potential candidates for pharmacological interference with the process. We demonstrate that Prohibitins (PHBs) are significantly enriched in the pseudopodia fraction derived from cancer cells, and knockdown of PHBs, as well as their chemical inhibition through Rocaglamide (Roc-A), efficiently reduces cancer cell migration.